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Shining new light on ancient malaria drugs

The PhD research of postdoctoral fellow John Woodland focused on providing new insights into the cellular localisation and targets of antimalarial drugs.

John Woodland, a student from the Department of Chemistry at UCT, recently graduated with a PhD. He is currently a postdoctoral research fellow in the Department of Molecular and Cell Biology.

Woodland’s PhD thesis was based on providing new insights into the cellular localisation and targets of antimalarial drugs. He collaborated with fellow scientists professors Roger Hunter, Peter Smith and Timothy Egan. Part of their work has already been published in Organic & Biomolecular Chemistry, a journal that is published by the Royal Society of Chemistry.

“We designed and synthesised novel fluorescent derivatives of the ancient antimalarial, quinine, and its diastereomer, quinidine. Surprisingly, no one has yet done a systematic survey of the subcellular localisation of these drugs within the malaria parasite, Plasmodium faciparum. We thoroughly evaluated these derivatives to ensure that they were suitable analogues of the parent molecules,” explains Woodland. “Finally, we performed live-cell super-resolution imaging to investigate the localisation of these fluorescent drug analogues in the parasite.

Not only has the article has been flagged as a 2016 “Hot Article” in Organic & Biomolecular Chemistry, which further highlights the significance of his research, it has also been selected to appear on the cover of the journal.

“These observations were able to resolve some long-running controversies, such as whether or not the drug localises to the parasite’s nucleus. That is why we decided to title our paper Shining new light on ancient drugs because that is exactly what we did.”

There is always more to learn

“For me, chemistry is thrilling, not only as an intellectual challenge to understand and predict the behaviour of molecules, but also in the direct way in which it is able to make a positive difference to our world,” says Woodland.

A fascination with the natural world and participation in science competitions and societies from an early age all contributed to his decision to pursue science. He speculates how his fascination with Lego may have laid the foundation for his later interest in chemistry.

“Lego is exactly like a chemistry model kit. In chemistry, small building blocks – the atoms – are used to construct an infinite array of more complex structures – molecules. Some of these are more useful or more beautiful than others,” he explains.

Woodland completed his BSc in chemistry and biochemistry in 2010 and enrolled for a BSc honours in chemistry the year after. He commenced with his MSc in 2012 and then upgraded his project to a PhD two years later, which he completed in August this year.

“The most important thing one learns at university is to think critically. You stop taking everything you read or hear at face value and question it instead. One learns how to learn, and how to find and synthesise information to generate new knowledge,” he says.

Music and molecules

Apart from the chemistry, music is Woodland’s other passion.

“I trained the UCT Choir, a student-run group and the most diverse ensemble on campus, for several years. We firmly entrenched the group in the musical life of the university.”

He now has his own singing group, VOX Cape Town, which was formed last year.

“My aim is to invigorate and enrich the musical life of the city through imaginative programming and staging to create intimate, immersive sensory experiences for audiences,” he says.

One of his doctoral supervisors, Professor Roger Hunter, also sings in the group.

“He advised me to try singing to my molecules when a particular reaction wasn’t working, much to the amusement of my lab colleagues,” chuckles Woodland. “I figured out what the problem was shortly after that.”

Woodland also voluntarily compiles and presents classical music programmes fortnightly on Fine Music Radio.

“Chemistry and music really aren’t that different – I constantly use analogies from the one to demonstrate or explain aspects of the other,” he says. “This illustrates the benefits of interdisciplinarity in our world and how unhelpful the persistent dichotomy between science and the arts really is.”

Science gives us a chance to bring about change

Woodland has a particular interest in infectious diseases.

“We are all aware of the enormous toll taken by the ‘big three’ on the developing world – malaria, tuberculosis and HIV/AIDS. For my PhD, I wanted to develop new tools which could be used to generate novel insights into antimalarial drug action that in turn could be exploited to inform the rational design of improved antimalarials.”

He spent a lot of time working on the Cinchona alkaloids, a special group of natural products that are isolated from the bark of the Cinchona tree.

“These molecules are extremely important in organic chemistry but also as antimalarials,” he says.

A dream of his is to make a positive impact on South African lives through research in science. He is also passionate about making science accessible and appealing through the effective communication of scientific ideas.

“This is particularly challenging in South Africa as our society is so heterogeneous. Unfortunately, scientific literacy is generally poor. In an age of science such as this, everybody ought to have a basic understanding of key scientific ideas and ought to think critically about the information they consume,” he says. “We, as scientists, have an obligation to convey our knowledge, passion and sense of wonder about the natural world to those without formal scientific training.”

What next?

“Science is exciting because there is always more to learn. It is just like music – even when you know the notes, every performance is different and one can spend years chasing that elusive perfect performance, or the perfect experiment that nails down an elegant hypothesis,” says Woodland.

“One learns to deal with a lot of uncertainty and failure but, ultimately, this stimulates creativity and imagination when one reaches the edge of knowledge.”

During his postgraduate years Woodland has been actively involved with outreach activities in the Department of Chemistry, mainly writing and directing a number of chemistry-themed plays for schoolchildren. For many years he also tutored and demonstrated for undergraduate chemistry courses at UCT.

In 2013 he participated in the first South African FameLab (described as Pop Idols for scientists) and represented UCT at the Falling Walls Competition in Berlin later that year. This culminated in him winning third place in the Young Innovator of the Year competition.

“These were excellent opportunities to engage with young scientists from around the world. I was fortunate to have these opportunities to fly South African’s flag on the world stage.”

He is unsure of what the future holds.

“At the moment I am very lucky to be satisfying both my head and my heart with science and music respectively. I will have to see where the journey takes me,” he says with a smile.

“I enjoy teaching and working with students so an academic career is appealing.”

He concludes, “As molecules and music are both important to me, I hope that it will ultimately be possible to combine the two in a novel way that makes a lasting impact on society.”